Posts Tagged ‘Alzheimer’s disease’


New studies show that elevated levels of a form of tau called p-tau217 can accurately distinguish Alzheimer’s disease from other forms of dementia, and perhaps even predict it.

by Kerry Grens

Three studies presented at the Alzheimer’s Association International Conference this week describe the performance of blood tests used to diagnose, and even predict, Alzheimer’s disease using circulating levels of a form of tau protein called p-tau217. The largest assessment of this approach, which included 1,402 participants, showed that circulating p-tau217 levels worked just as well at detecting Alzheimer’s as standard PET scans and tests of cerebrospinal fluid.

“This blood test very, very accurately predicts who’s got Alzheimer’s disease in their brain, including people who seem to be normal,” Michael Weiner, an Alzheimer’s disease researcher at the University of California, San Francisco, who was not involved in the study, tells The New York Times. “It’s not a cure, it’s not a treatment, but you can’t treat the disease without being able to diagnose it. And accurate, low-cost diagnosis is really exciting, so it’s a breakthrough.”

A blood test could help identify people on track to develop Alzheimer’s early on—and perhaps get them enrolled in drug trials aimed at finding an effective treatment for the disease. Scientists have pursued a number of potential circulating biomarkers, such as amyloid-β, to find those that can reliably diagnose Alzheimer’s disease or predict its development, but to date none have come to market.

High levels of tau or its phosphorylated form, p-tau, have emerged as promising biomarker candidates because they may indicate the presence of damaging structures known as neurofibrillary tangles in the brain.

The large study on one type of p-tau, p-tau217, published in JAMA July 28 to coincide with the presentation at the meeting, was a collection of three experiments using a blood test developed by Eli Lilly (some of the coauthors work for the company). In one assessment of several hundred Swedes, the test accurately distinguished patients who had Alzheimer’s from those with other forms of dementia with 89–98 percent accuracy. “That’s pretty good. We’ve never seen that” precision before, Maria Carrillo, the Alzheimer’s Association’s chief science officer, tells the Associated Press.

In another assessment of the Eli Lilly test, which included hundreds of related individuals, some of whom have a gene that causes Alzheimer’s, p-tau217 levels in the blood aligned with the genetics, even decades before cognitive impairment is likely to begin.

Another study presented at the conference found a p-tau217 blood test could accurately distinguish Alzheimer’s patients from those with frontotemporal lobar degeneration, according to a conference press release. And a third presentation of a study by Suzanne Schindler of Washington University in St. Louis and her colleagues reported that circulating p-tau217 was superior to another form that’s been studied as a potential biomarker, p-tau181, as a proxy for amyloid accumulation in the brain.

“I personally find it very reassuring that these different groups are using different types of assays and getting the same result,” Schindler tells the Times. “It looks real. It looks like 217 has tremendous promise as a blood test for Alzheimer’s disease, and it is likely to correspond with the symptoms.”

Speaking to The Guardian, Clive Ballard, who studies age-related disease at the University of Exeter Medical School and who was not involved in these projects, says, “further validation in people from more routine clinical settings are still needed, and a lot of work will be needed to achieve standardisation of the test across laboratories—so it could still be at least five years before we see an accurate blood biomarker test for dementia in the clinic.”

https://www.the-scientist.com/news-opinion/experimental-blood-test-could-flag-alzheimers-67779?utm_campaign=TS_DAILY%20NEWSLETTER_2020&utm_medium=email&_hsmi=92321648&_hsenc=p2ANqtz-8ayk91AfO8kNKldfK3kfssyQf2GRuKPsOimQKjhl3hz5Ap-KFfFI0molaN5LwimzBJw9JHyX8TCowcon5V50G5hr5ErA&utm_content=92321648&utm_source=hs_email

The dopaminergic agonist Neupro appeared to improve frontal cognitive functions and activities of daily living among patients with mild to moderate Alzheimer’s disease, according to study results published in JAMA Network Open.

“Some early attempts have been carried out using dopaminergic drugs, such as L-dopa or selegiline, in samples of patients with Alzheimer’s disease at different stages of the disease, with some controversial results,” Giacomo Koch, MD, PhD, of the department of behavioral and clinical neurology at Santa Lucia Foundation Scientific Institute for Research, Hospitalization and Healthcare in Rome, and colleagues wrote. “More recently, experimental studies in animal models of Alzheimer’s disease showed that dopaminergic agonists may reduce amyloid deposition and improve memory and that the degeneration of dopaminergic neurons in the ventral tegmental area contributes to memory deficits. It has also been shown that in the early stages of Alzheimer’s disease, dopaminergic agonists improve cholinergic transmission and cortical plasticity likely by acting on the dopaminergic projections over the frontal cortex.”

This prior evidence suggested novel implications for therapies based on dopaminergic stimulation among patients with mild to moderate Alzheimer’s disease, according to the investigators. Thus, they sought to determine whether dopaminergic agonist therapy would affect cognitive functions among this patient population.

In the current phase 2, monocentric, randomized, double-blind, placebo-controlled trial conducted in Italy and funded by the Alzheimer’s Drug Discovery Foundation, Koch and colleagues enrolled 94 patients (mean age, 73.9 years) with mild to moderate Alzheimer’s disease between September 2017 and December 2018. The intervention comprised use of a Neupro (rotigotine, UCB) 2 mg transdermal patch for 1 week, followed by a 4 mg patch for 23 weeks among 47 patients or a placebo transdermal patch for 24 weeks among 47 patients. Change from baseline on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale served as the primary end point. Secondary end points included changes in Frontal Assessment Battery, Alzheimer’s Disease Cooperative Study-Activities of Daily Living and Neuropsychiatric Inventory scores. The researchers used transcranial magnetic stimulation combined with electroencephalography to evaluate prefrontal cortex activity.

A total of 78 patients completed the study. Results showed rotigotine compared with placebo had no significant effect on the primary end point, with an estimated mean change in Alzheimer’s Disease Assessment Scale-Cognitive Subscale score of 2.92 (95% CI, 2.51-3.33) among the rotigotine group and 2.66 (95% CI, 2.31-3.01) among the placebo group. The researchers reported significant estimated mean changes for the secondary outcomes between groups for Alzheimer Disease Cooperative Study-Activities of Daily Living score, which was 3.32 (95% CI, 4.02 to 2.62) among the rotigotine group and 7.24 (95% CI, 7.84 to 6.64) among the placebo group. Frontal Assessment Battery score was 0.48 (95% CI, 0.31-0.65) among the rotigotine group and 0.66 (95% CI, 0.80 to 0.52) among the placebo group. Koch and colleagues observed no longitudinal change in Neuropsychiatric Inventory scores for either group. Neurophysiological analysis of electroencephalography results revealed increased prefrontal cortical activity among the rotigotine group but not the placebo group. Patients in the rotigotine group were more likely to experience adverse events than the placebo group, and 11 patients dropped out compared with five, respectively.

“This study provides novel evidence that drugs acting on the dopaminergic system may be helpful to improve cognitive functions related to the frontal lobe activity,” Koch told Healio Psychiatry. “We hope that this research will expand Alzheimer’s disease therapy to drugs acting on different neurotransmission systems, such as the dopaminergic one, in addition to the cholinergic drugs.”

https://www.healio.com/news/psychiatry/20200715/neupro-may-reduce-cognitive-dysfunction-among-patients-with-alzheimers-disease?utm_source=ADDF&utm_campaign=e9d85ea654-EMAIL_CAMPAIGN_2019_11_18_10_21_COPY_01&utm_medium=email&utm_term=0_cc5f9da121-e9d85ea654-97060793


Risk is 1.8 times higher for overweight women and 2.5 times higher for men

by Ella Pickover

People who are overweight in early adult life may be more prone to dementia in later life, a study suggests.

Those aged 20 to 49 who have a high body mass index have a higher risk of dementia later on, the authors said.

Researchers from Columbia University in the US studied data on more than 5,000 adults.

Compared with women who had a normal BMI, those who were overweight had a 1.8 times higher risk of dementia later on in life.

Obese women had a 2.5 times higher risk.

For men, dementia risk was 2.5 times higher among those who were obese in early adulthood, according to the findings presented to the Alzheimer’s Association International Conference.

An association was found between being overweight or obese in mid-life – classed in the study as people aged 50 to 69 – among men but not women.

Both men and women have a higher chance of dementia if they are obese in later life, the researchers found.

Commenting on the study, Dr Rosa Sancho, head of research at Alzheimer’s Research UK, said: “This study links a higher BMI in early adulthood with an increased risk of dementia later in life and underlines the importance of maintaining a healthy weight to help support a healthy brain.”

But more studies are needed to examine the link in more detail, she said, adding: “We know that diseases that cause dementia get under way in the brain many years before symptoms start to show. Studies looking at our lifestyle in early adulthood are important to help us build a picture of the factors that could impact our brain health as we age.”

Fiona Carragher, director of research and influencing at Alzheimer’s Society, added: “A healthy and balanced lifestyle is an important step towards reducing the risk of dementia later in life.

“Previous research we’ve supported, such as the 2017 Lancet commission, has shown that obesity in mid-life may increase dementia risk, so it’s interesting to see a study that shows this may also be the case in younger people too. But this can’t tell us if high BMI is a direct cause of dementia, there could be other factors at play.

“The number of people living with dementia is set to rise to one million by 2025 so it’s becoming increasingly urgent that we find ways to prevent people developing the condition in the first place.

“We can all take steps towards a healthy lifestyle, whether it’s by watching our diets or making the most of the sunny days and getting outside for a walk – it’s never too late, or early, to make a change.

“Research funding also plays a vital role here, hit badly by the current pandemic – so it’s critical that the government commits to their pledge to double life-saving research funding for the chronically under-funded field of dementia.”

https://www.independent.co.uk/news/uk/home-news/bmi-early-adulthood-increased-dementia-risk-us-a9645101.html


Research by 2015 ADDF-Harrington Scholar Jerri Rook, Ph.D. of Vanderbilt University leads to licensing agreement to develop drugs that improve memory.

A recently announced licensing agreement between drug maker Acadia Pharmaceuticals and Vanderbilt University represents a major milestone for the ADDF-Harrington Scholar Award Program, which provided funding and pharmaceutical expertise to support the research in the early phases. Acadia and Vanderbilt will collaborate to develop and commercialize novel drug candidates targeting synaptic receptors in the brain, long thought to play a key role in Alzheimer’s disease.

“This type of licensing agreement is precisely the goal of the ADDF-Harrington partnership,” said Dr. Andrew A. Pieper, Harrington Discovery Institute Director of Neurotherapeutic Discovery. “We bridge the gap between academia, where many great medical ideas are born, and industry, where these ideas can be guided through the costly and complex process of transforming them into new medicines for patients.”

Vanderbilt University principal investigator Jerri Rook, Ph.D. and her Vanderbilt University Medical Center physician collaborator Dr. Paul Newhouse received the 2015 ADDF-Harrington Scholar Award. The award provided funding and expertise in formulation and interpretation of safety pharmacology and toxicology data from experienced drug development professionals.

The compounds covered by the agreement work by activating muscarinic M1 receptors in the brain in a unique way that increases their responsiveness to a neurotransmitter called acetylcholine, which plays a critical role in regulating memory and cognition.

“We are excited about the commercial support for the important work of Dr. Rook and her colleagues that we hope will lead to an effective and safe treatment for people with Alzheimer’s disease,” said Dr. Howard Fillit, ADDF Founding Executive Director and Chief Science Officer.

As explained by Dr. Rook, researchers have long theorized that this mechanism could effectively treat memory loss in Alzheimer’s disease and other brain disorders, but intolerable side effects have barred their use—at least so far. “Our focus has been on discovering and developing compounds that have the desired treatment benefits without the unwanted side effects. We have now optimized this in a mouse model of Alzheimer’s disease and are very much looking forward to seeing how they perform in human studies,” said Dr. Rook. The lead compound has entered Phase I clinical trials with support from the ADDF.

About the Alzheimer’s Drug Discovery Foundation (ADDF)

The Alzheimer’s Drug Discovery Foundation is the only public charity solely focused on funding the development of drugs for Alzheimer’s disease, employing a venture philanthropy model to support research in academia and the biotech industry. Through the generosity of its donors, the ADDF has awarded more than $150 million to fund over 626 Alzheimer’s drug discovery programs and clinical trials in 19 countries. To learn more, please visit: https://www.alzdiscovery.org/.

About the Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, Ohio—part of The Harrington Project for Discovery & Development—aims to advance medicine and society by enabling the most inventive scientists to turn their discoveries into medicines that improve human health. The Institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a “Better World.”

SOURCE Alzheimer’s Drug Discovery Foundation

https://www.prnewswire.com/news-releases/alzheimers-drug-discovery-foundation-addf-and-harrington-discovery-institute-partnership-helps-move-promising-alzheimers-research-from-bench-toward-bedside-301096316.html?tc=eml_cleartime


Eugenia Trushina, PhD: Mitochondria as a Therapeutic Target for Alzheimer

The Alzheimer’s Drug Discovery Foundation (ADDF) and Harrington Discovery Institute at University Hospitals have granted Eugenia Trushina, Ph.D., of Mayo Clinic Rochester, the ADDF-Harrington Scholar Award.

Dr. Trushina has been awarded $600,000 for her late stage preclinical research on new drug candidates that show promise in restoring mitochondrial function. In addition to funding, she will receive in-depth drug development support to help maximize her project’s potential for clinical success.

“The ADDF-Harrington partnership helps scientists move academic discoveries from their labs toward clinical studies, and eventually into the clinic to improve the lives of people living with and at risk of Alzheimer’s,” said Dr. Howard Fillit, the ADDF’s Founding Executive Director and Chief Science Officer. “The mitochondria, which are the powerhouses of the cell, are a promising new target in the fight to combat this devastating disease.”

Dr. Trushina has shown that restoring function in mitochondria may delay the onset or slow the progression of Alzheimer’s disease. The compounds she and her team have developed have shown a positive effect in both symptomatic and pre-symptomatic models of Alzheimer’s.

“Supporting this innovative therapeutic approach for patients with Alzheimer’s disease represents our dedication to developing new classes of medicines that are not otherwise traditionally pursued in the field,” said Dr. Andrew Pieper, Director of the Neurotherapeutics Center of the Harrington Discovery Institute and University Hospitals Morley-Mather Chair in Neuropsychiatry.

Dr. Trushina’s research was selected through a competitive process, based on its potential to advance towards the clinic as a novel approach to treat, prevent, or cure Alzheimer’s disease and related dementias. Collaboration between the ADDF and Harrington Discovery Institute for this award provides recipients with both research funding and expert guidance in order to efficiently bridge the gap between academia and pharma.

“We are in our seventh year of collaborating with the ADDF to address this major unmet medical need,” said Jonathan Stamler, MD, President, Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation and Professor of Medicine at University Hospitals and Case Western Reserve University. “This partnership leverages our combined expertise and resources to give the science the best chance of advancing towards a cure for Alzheimer’s disease.”

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About the Alzheimer’s Drug Discovery Foundation (ADDF)

The Alzheimer’s Drug Discovery Foundation is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer’s disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer’s, employing a venture philanthropy model to support research in academia and the biotech industry. Through the generosity of its donors, the ADDF has awarded more than $150 million to fund over 626 Alzheimer’s drug discovery programs and clinical trials in 19 countries. To learn more, please visit: https://www.alzdiscovery.org/

About the Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, Ohio–part of The Harrington Project for Discovery & Development–aims to advance medicine and society by enabling our nation’s most inventive scientists to turn their discoveries into medicines that improve human health. The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a “Better World.”

About the Harrington Project for Discovery & Development

The Harrington Project for Discovery & Development (The Harrington Project), founded in late February 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines.

https://www.eurekalert.org/pub_releases/2020-07/addf-aah070720.php


A new study has found a new link between regular aerobic exercise and improved cognitive function in brain regions associated with Alzheimer’s disease.

By Nick Lavars

Previous research has shown us how regular exercise can be beneficial for cognitive function and help stave off the brain degeneration associated with dementia and Alzheimer’s, but scientists continue to learn more about the mechanisms at play. The latest discovery in this area comes courtesy of researchers from the University of Wisconsin (UW), who have published a new study describing a relationship between regular aerobic exercise and a reduced vulnerability to Alzheimer’s among high-risk adults.

More and more research is establishing stronger and stronger links between exercise and the prevention or slowing of Alzheimer’s and dementia. Last September, one study found that a regime of regular aerobic exercise could slow the degeneration of the hippocampus, while another from early in 2019 found that a hormone released during exercise can improve brain plasticity and memory.

For the new study, the UW researchers enlisted 23 subjects, with the participants all cognitively healthy young adults but with a heightened risk of Alzheimer’s due to family history and genetics. All lived what the researchers describe as a sedentary lifestyle and were first put through examinations to assess their cardiorespiratory fitness, cognitive function, typical daily physical activity, and brain glucose metabolism, which is considered a measure of neuronal health.

From there, half of the subjects were given information about how to lead a more active lifestyle, but were then left to their own devices. The other half of the group was given a personal trainer and put through a treadmill training program described as “moderate intensity,” involving three sessions a week across 26 weeks.

Unsurprisingly, the active group demonstrated improved cardio fitness and took on less sedentary lifestyles once the training program had finished. But in addition, they scored higher on cognitive tests of executive functioning, which is the capacity of the brain to plan, pay attention, remember instructions and multitask. Executive function is known to deteriorate during the onset of Alzheimer’s.

“This study is a significant step toward developing an exercise prescription that protects the brain against AD, even among people who were previously sedentary,” explains lead investigator Ozioma C. Okonkwo.

In addition to this improved executive function, brain scans also revealed some marked differences in brain glucose metabolism in the posterior cingulate cortex, a region again linked with Alzheimer’s.

“This research shows that a lifestyle behavior – regular aerobic exercise – can potentially enhance brain and cognitive functions that are particularly sensitive to the disease,” says Okonkwo. “The findings are especially relevant to individuals who are at a higher risk due to family history or genetic predisposition.”

With the sample size on the small side, the researchers are now working towards larger studies with more subjects to see if their findings can be replicated.

The research was published in the journal Brain Plasticity.

https://newatlas.com/medical/aerobic-exercise-risk-alzheimers-vulnerable-adults/


Pet scans comparing brains with Alzheimer’s with healthy brains. The researchers used PET scans to study the brains of 32 people with early Alzheimer’s. Photograph: Jonathan Selig/Getty Images
Research suggests tangles of tau could be used to predict how much shrinkage will occur and where

Tangles of a protein found inside the brain cells of people with Alzheimer’s disease can be used to predict future brain shrinkage, research suggests.

In healthy people, a protein called tau is important in supporting the internal structure of brain cells. However, in those with Alzheimer’s, chemical changes take place that cause the protein to form tangles that disrupt the cells. Such tangles have previously been linked to a loss of brain cells.

Now scientists have used imaging techniques to track the extent of tau tangles in the brains of those with early signs of Alzheimer’s, revealing that levels of the protein predict not only how much brain shrinkage will subsequently occur, but where.

“Our study supports the notion that tau pathology accumulates upstream of brain tissue loss and clinical symptoms,” said Prof Gil Rabinovici, a co-author of the research from the University of California, San Francisco.

A number of drugs targeting tau tangles are currently in clinical trials, including some that aim to interfere with the production of tau in the brain or its spread between cells.

Dr Renaud La Joie, another author of the research, said the findings suggested the imaging technique could prove valuable both in choosing which patients to enrol to test such drugs and in monitoring whether the drugs work.

Dr Laura Phipps, of Alzheimer’s Research UK, said: “The ability to track tau in the brain will be critical for testing treatments designed to prevent the protein causing damage, and the scans used in this study could be an important tool for future clinical trials.”

Writing in the journal Science Translational Medicine, La Joie and colleagues report how they used an imaging technique called positron emission tomography (Pet) to study the brains of 32 people aged between 49 and 83 who were in the early stages of showing Alzheimer’s symptoms.

Pet imaging involves injecting patients with a substance that contains a radioactive atom. The area in which the substance clusters shows up in subsequent scans.

The scientists used one substance that attaches to plaques of a protein in the brain known as beta amyloid, a hallmark of Alzheimer’s disease, and another recently developed substance that attaches to tau tangles.

They took a Pet scan at the start of the study, as well as an MRI, which reveals the structure of the brain. A second MRI was taken 15 months later to track brain atrophy.

The results reveal the level and location of tau tangles shown by the Pet scan at the outset were closely linked to shrinkage of grey matter in the brain, both in terms of the degree of shrinkage and its location. Such patterns explained about 40% of the variation in shrinkage. By contrast, there was little sign of a link between brain shrinkage and the extent of beta amyloid shown by Pet scan.

The findings held even when the thickness of the brain’s grey matter at the start of the study was taken into account, and when the age of participants was considered.

Although previous research has suggested brain atrophy shows a stronger link to tau tangles than beta amyloid, the team say the findings were still a surprise. “We were amazed by how well tau predicted not only the degree of atrophy overall, but the precise location of atrophy in individual patients,” said La Joie.

But, he added, the lack of a link to signs of beta amyloid does not mean those plaques are not harmful. “It is extremely rare to see significant amounts of tau tangles across the brain in patients with no amyloid: for some reason, amyloid seems almost necessary for tau to build up in the cortex,” said La Joie.

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The study has limitations, including that the Pet scan gives only an indirect measure of levels of tau and beta amyloid, and the tracking substances might not bind only to those proteins.

“This relatively small study adds to evidence that tau may drive the death of brain cells, and could explain why symptoms get worse as tau spreads through the brain,” said Phipps. “While the majority of volunteers in the study were under the age of 65, making it harder to generalise the findings to everyone with the disease, the study highlights the importance of focusing future research efforts on the tau protein.”

https://www.theguardian.com/science/2020/jan/01/protein-tangles-in-alzheimers-patients-could-help-predict-brain-shrinkage


Dr. Moir’s radical and iconoclastic theories defied conventional views of the disease. But some scientists were ultimately won over.

By Gina Kolata

Robert D. Moir, a Harvard scientist whose radical theories of the brain plaques in Alzheimer’s defied conventional views of the disease, but whose research ultimately led to important proposals for how to treat it, died on Friday at a hospice in Milton, Mass. He was 58.

His wife, Julie Alperen, said the cause was glioblastoma, a type of brain cancer.

Dr. Moir, who grew up on a farm in Donnybrook, a small town in Western Australia, had a track record for confounding expectations. He did not learn to read or write until he was nearly 12; Ms. Alperen said he had told her that the teacher at his one-room schoolhouse was “a demented nun.” Yet, she said, he also knew from age 7 that he wanted to be a scientist.

Dr. Moir succeeded in becoming a researcher who was modest and careful, said his Ph.D. adviser, Dr. Colin Masters, a neuropathologist at the University of Melbourne. So Dr. Masters was surprised when Dr. Moir began publishing papers proposing an iconoclastic rethinking of the pathology of Alzheimer’s disease.

Dr. Moir’s hypothesis “was and is a really novel and controversial idea that he alone developed,” Dr. Masters said.

“I never expected this to come from this quiet achiever,” he said.

Dr. Moir’s theory involved the protein beta amyloid, which forms plaques in the brains of Alzheimer’s patients.

Conventional wisdom held that beta amyloid accumulation was a central part of the disease, and that clearing the brain of beta amyloid would be a good thing for patients.

Dr. Moir proposed instead that beta amyloid is there for a reason: It is the way the brain defends itself against infections. Beta amyloid, he said, forms a sticky web that can trap microbes. The problem is that sometimes the brain goes overboard producing it, and when that happens the brain is damaged.

The implication is that treatments designed to clear the brain of amyloid could be detrimental. The goal would be to remove some of the sticky substance, but not all of it.

The idea, which Dr. Moir first proposed 12 years ago, was met with skepticism. But he kept at it, producing a string of papers with findings that supported the hypothesis. Increasingly, some of the doubters have been won over, said Rudolph Tanzi, a close friend and fellow Alzheimer’s researcher at Harvard.

Dr. Moir’s unconventional ideas made it difficult for him to get federal grants. Nearly every time he submitted a grant proposal to the National Institutes of Health, Dr. Tanzi said in a phone interview, two out of three reviewers would be enthusiastic, while a third would simply not believe it. The proposal would not be funded.

But Dr. Moir took those rejections in stride.

“He’d make a joke about it,” Dr. Tanzi said. “He never got angry. I never saw Rob angry in my life. He’d say, ‘What do we have to do next?’ He was always upbeat, always optimistic.”

Dr. Moir was supported by the Cure Alzheimer’s Fund, and he eventually secured some N.I.H. grants.

Dr. Moir first came to the United States in 1994, when Dr. Tanzi was looking for an Alzheimer’s biochemist to work in his lab. Working with the lab as a postdoctoral fellow and later as a faculty member with his own lab, Dr. Moir made a string of major discoveries about Alzheimer’s disease.

For example, Dr. Moir and Dr. Tanzi found that people naturally make antibodies to specific forms of amyloid. These antibodies protect the brain from Alzheimer’s but do not wipe out amyloid completely. The more antibodies a person makes, the greater the protection against Alzheimer’s.

That finding, Dr. Tanzi said, inspired the development of an experimental drug, which its manufacturer, Biogen, says is helping to treat some people with Alzheimer’s disease. Biogen plans to file for approval from the Food and Drug Administration.

Robert David Moir was born on April 2, 1961, in Kojonup, Australia, to Mary and Terrence Moir, who were farmers. He studied the biochemistry of Alzheimer’s disease at the University of Western Australia before joining Dr. Tanzi’s lab.

Once he learned to read, Ms. Alperen said, he never stopped — he read science fiction, the British magazine New Scientist and even PubMed, the federal database of scientific publications.

“Rob had an encyclopedic knowledge of the natural world,” she said.

He shared that love with his family, on frequent hikes and on trips with his young children to look for rocks, insects and fossils. He also played Australian-rules football, which has elements of rugby as well as American football, and helped form the Boston Demons Australian Rules Football Team in 1997, his wife said.

In addition to his wife, with whom he lived in Sharon, Mass., Dr. Moir’s survivors include three children, Alexander, Maxwell and Holly Moir; a brother, Andrew; and a sister, Catherine Moir. His marriage to Elena Vaillancourt ended in divorce.

A new paper in the Journal of Neuropathology & Experimental Neurology finds a gene that may help explain a large part of the genetic risk for developing Alzheimer disease.

Late-onset Alzheimer disease, the most common form of the illness, is a devastating neurological condition with aspects of heritable risk that are incompletely understood. Unfortunately, the complexity of the human genome and shortcomings of earlier research are limiting factors, so that some genetic phenomena were not surveyed completely in prior studies. For example, there are many incompletely mapped genomic regions, and areas with repetitive sequences, that could not be studied previously.

Although Alzheimer’s is known to be largely heritable, a substantial proportion of the actual genetic risk for the disease has remained unexplained, despite extensive studies. This knowledge gap is known to researchers are the “missing (or hidden) heritability” problem. For example, while heritability explained 79% of late-onset Alzheimer disease risk in a Swedish twin study, common risk variants identified by pervious genetic studies explained only 20% to 50% of late-onset Alzheimer disease. In other words, a relatively large amount of genetic influence on late-onset Alzheimer disease risk was not explained by prior genetic studies.

Recent advances in sequencing technologies have enabled more comprehensive studies. Such developments allow for more precise and accurate identification of genetic material than was available in earlier gene variant studies.

In the present study, researchers analyzed Alzheimer’s Disease Sequencing Project data derived from over 10,000 people (research volunteers who agreed to have their genetic data evaluated in combination with their disease status), with the goal of identifying genetic variation associated with late-onset Alzheimer disease.

Preliminary results found evidence of late-onset Alzheimer disease -linked genetic variation within a segment of a gene called Mucin 6. Although the underlying mechanisms are mostly still unknown, researchers here believe that it’s possible to draw credible and testable hypotheses based on these results. For example, the genetic variant that was associated with Alzheimer’s disease risk may implicate a biochemical pathway in the brain that then represents a potential therapeutic target, a topic for future studies.

Corresponding authors were Yuriko Katsumata and Peter Nelson, both from the University of Kentucky. Dr. Nelson said of this study, “Our findings were made in a group of patients that is relatively small for a genetics study–some recent studies included hundreds of thousands of research subjects! That small sample size means two things: first, we should exercise caution and we need to make sure the phenomenon can be replicated in other groups; and second, it implies that there is a very large effect size–the genetic variation is strongly associated with the disease.”

https://eurekalert.org/pub_releases/2019-11/oupu-nar111819.php

New research has found that people who are illiterate, meaning they never learned to read or write, may have nearly three times greater risk of developing dementia than people who can read and write. The study is published in the November 13, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

According to the United States Department of Education, approximately 32 million adults in the country are illiterate.

“Being able to read and write allows people to engage in more activities that use the brain, like reading newspapers and helping children and grandchildren with homework,” said study author Jennifer J. Manly, Ph.D., of Columbia University Vagelos College of Physicians and Surgeons in New York. “Previous research has shown such activities may reduce the risk of dementia. Our new study provides more evidence that reading and writing may be important factors in helping maintain a healthy brain.”

The study looked at people with low levels of education who lived in northern Manhattan. Many were born and raised in rural areas in the Dominican Republic where access to education was limited. The study involved 983 people with an average age of 77. Each person went to school for four years or less. Researchers asked each person, “Did you ever learn to read or write?” Researchers then divided people into two groups; 237 people were illiterate and 746 people were literate.

Participants had medical exams and took memory and thinking tests at the beginning of the study and at follow-up appointments that occurred every 18 months to two years. Testing included recalling unrelated words and producing as many words as possible when given a category like fruit or clothing.

Researchers found of the people who were illiterate, 83 of 237 people, or 35 percent, had dementia at the start of the study. Of the people who were literate, 134 of 746 people, or 18 percent, had dementia. After adjusting for age, socioeconomic status and cardiovascular disease, people who could not read and write had nearly a three times greater chance of having dementia at the start of the study.

Among participants without dementia at the start of the study, during follow-up an average of four years later, 114 of 237 people who were illiterate, or 48 percent, had dementia. Of the people who were literate, 201 of 746 people, or 27 percent, had dementia. After adjusting for age, socioeconomic status and cardiovascular disease, researchers found that people who could not read and write were twice as likely to develop dementia during the study.

When researchers evaluated language, speed, spatial, and reasoning skills, they found that adults who were illiterate had lower scores at the start of the study. But their test scores did not decline at a more rapid rate as the study progressed.

“Our study also found that literacy was linked to higher scores on memory and thinking tests overall, not just reading and language scores,” said Manly. “These results suggest that reading may help strengthen the brain in many ways that may help prevent or delay the onset of dementia.”

Manly continued, “Even if they only have a few years of education, people who learn to read and write may have lifelong advantages over people who never learn these skills.”

Manly said future studies should find out if putting more resources into programs that teach people to read and write help reduce the risk of dementia.

A limitation of the study was that researchers did not ask how or when literate study participants learned to read and write.

The study was supported by the National Institutes of Health and National Institute on Aging.

Story Source:

Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

Journal Reference:

Miguel Arce Rentería, Jet M.J. Vonk, Gloria Felix, Justina F. Avila, Laura B. Zahodne, Elizabeth Dalchand, Kirsten M. Frazer, Michelle N. Martinez, Heather L. Shouel, Jennifer J. Manly. Illiteracy, dementia risk, and cognitive trajectories among older adults with low education. Neurology, 2019; 10.1212/WNL.0000000000008587 DOI: 10.1212/WNL.0000000000008587

https://www.sciencedaily.com/releases/2019/11/191114180033.htm